Managing Chemotherapy Side Effects
Inappetence is not an uncommon symptom in dogs and cats with cancer. This may be secondary to the cancer itself (like gastrointestinal lymphoma in cats) or treatment with chemotherapy. It is unclear if chemotherapy causes altered taste and smell in pets on chemotherapy. Ideally, we should make sure our cancer patients are eating an adequate amount of food. Offering different types and consistencies of food, adding flavoring (such as sweet or salty items), altering protein and/or fat content, feeding a variety of foods, and offering food in a non-metal bowl which can reduce the metallic aftertaste. Pharmacologic intervention may be necessary in some patients. The most commonly used appetite stimulants in pets are:
1. Mirtazapine
- Dogs: 3.75-30 mg PO every 24 hours, or 1-1.3 mg/kg not to exceed 30 mg/day
- Cats: 1.88-3.75 mg PO every 24-48 hours, or 1.5” strip of transdermal ointment daily
2. Entyce® (capromorelin)
- Dogs: 3mg/kg PO once daily
- Cats: Cags: 2 mg/kg PO once daily OFF LABEL USE
- Reports of hypotension and bradycardia
- Randomized controlled trial showed limited clinical or clinical pathology findings (Wofford JA et al. Evaluation of the safety of daily administration of capromorelin in cats. J Vet Pharmacol Ther. 2018 Apr;41(2):324-333)
Acupuncture and acupressure can also be an excellent way to stimulate appetite. A veterinarian trained in acupuncture can treat the patient, but the owners can perform acupressure at home. Shan gen is a classical acupuncture point that is used to stimulate appetite. Shan gen is located just caudal to the nose on the haired skin along midline (see photo below). The area can be rubbed gently with the tip of the finger for approximately 20 seconds.
Chemotherapy can also cause nausea and/or vomiting in pets. Nausea and vomiting typically occur 2-3 days after treatment and it occurs due to several different mechanisms. The timing relative to chemotherapy is anticipatory, acute, and delayed. The physiology of vomiting is controlled by neural and hormonal influences. Antiemetics block neurotransmitters at the central (CRTZ, emetic center) and peripheral (gastrointestinal tract) levels.
Specific treatments include:
-
- Diet change: Pets experiencing nausea/vomiting should first be held off food to let the gastrointestinal tract rest. Thereafter, the pet should be offered water, then fed smaller, more frequent meals. I typically recommend a bland diet designed for intestinal upset (such as Hill’s i/d) or boiled chicken and rice, pasta, low fat cottage cheese, and eggs.
- Omeprazole: Proton pump inhibitor used to treat gastritis and gastrointestinal ulceration by reducing stomach acid production. It is preferred over famotidine due to superior efficacy.
- Dogs & cats: 1 mg/kg PO q 12-24 hours
- Ondansetron: Serotonin antagonist
- Dogs: 0.5-1 mg/kg PO q 8-12 hours
- Cats: 0.1-1 mg/kg PO q 6-12 hours
- Metoclopramide: Dopamine antagonist. I typically do not use metoclopramide unless I suspect the symptoms are due to ileus which is caused by vincristine. In these cases I typically add metoclopramide for its prokinetic properties. Vincristine induced ileus can be quite delayed so if symptoms develop within 2 weeks of treatment with vincristine and appear prolonged, a trial with metoclopramide is reasonable.
- Dogs: 0.2-0.5 mg/kg PO q 8 hours
- Maropitant (Cerenia): Neurokinin antagonist FDA approved for use in dogs and cats (SC). Cerenia is my drug of choice for patients on chemotherapy. I find it to be most effective and easiest to dose.
- Dogs: 2 mg/kg PO q 24 hours
- Cats: 1 mg/kg P q14 hours OFF LABEL USE
| Drug name | Mechanism of Action | Dosage | Frequency | Route |
|---|---|---|---|---|
| Metoclopramide | Prokinetic agent, dopamine antagonist, 5-HT3 blockade at high dosage | 0.2-0.5 mg/kg | q6-8 h | PO/SQ/IV |
| Ondansetron (Zofran) | 5-HT3 receptor antagonist | 0.3-1.0 mg/kg | q12 hr | PO/SQ/IM/IV |
| Maropitant (Cerenia®) | Neurokinin-1 receptor antagonist | 1 mg/kg
2 mg/kg |
q24h
q24h |
SQ
PO |
| Omeprazole (Prilosec®) | Proton pump inhibitor | 0.5-1 mg/kg | q12-24h | PO |
| Mirtazapine | Tetracycline antidepressant, 5-HT3 antagonist | 3.75-30mg
1.5” strip |
q24h
q24h |
PO
TD cats |
Diarrhea can be a potential complication of chemotherapy and targeted therapies in dogs and cats. It is a result of damage to the lining of the intestinal tract. Diarrhea can also be a result of the primary cancer if it is intestinal in origin.
Pets with diarrhea should be offered ample water and liquids to prevent dehydration. Adding water or low sodium chicken broth to food is a good way to increase their intake. When diarrhea develops, smaller, more frequent meals should be offered. The diet should be low fat and similar to those used for nausea and vomiting. As opposed to diarrhea, it should be noted that cats can develop constipation secondary to vincristine administration (due to ileus).
Pharmacologic options include:
-
- Metronidazole: Metronidazole and antibacterial, antiprotozoal and anti-inflammatory effects. It has a very bitter, unpleasant taste so liquids are often not well tolerated. I use the lowest dose possible in my patients and find it effective in most cases. At higher doses, metronidazole can cause neurotoxicity.
- Dogs: 10-15 mg/kg PO q 12-24 hours
- Cats: 10-15 mg/kg PO q 12 hours or 15-25 mg/kg PO q 24 hours. Compounded tiny tablets are an excellent option for cats, or ~1/4 of a 250 mg tablet q12-24 hours.
- Tylosin: Tylosin is a macrolide antibiotic in powder form. 1/8 teaspoon of powder contains approximately 325 mg of tylosin. Tylosin can be added to the pet’s food, but the powder is bitter and unpalatable.
- Dogs: 20-25 mg/kg PO q 12-24 hours
- Probiotics: Probiotics can be helpful in the management of diarrhea. My first choice is the Proviable Forte kit. The kit includes capsules and a paste that contains kaolin and pectin to help firm stool and soothe the GI tract in cases of acute diarrhea.
- Metronidazole: Metronidazole and antibacterial, antiprotozoal and anti-inflammatory effects. It has a very bitter, unpleasant taste so liquids are often not well tolerated. I use the lowest dose possible in my patients and find it effective in most cases. At higher doses, metronidazole can cause neurotoxicity.
- Loperamide: GI opioid motility modifier. I do not use this medication to treat diarrhea. It should not be in dogs with MDR1 genetic mutations.
The goal of chemotherapy is to balance effectively treating cancer and minimizing toxicity. Neutropenia is a known complication to treatment with chemotherapy and it can be life-threatening. Smaller dogs (<~10-15 kg) are most likely to develop neutropenia. The drugs most commonly implicated in neutropenia include doxorubicin, vincristine and lomustine. In the vast majority of cases, neutropenia occurs 5-7 days after treatment. The exception is carboplatin which has a delayed nadir that usually occurs between 14-21 days. Neutropenia does not need to be addressed unless the count is between 500-1000 cell/uL, and more recent studies suggest a cut off of 750/uL. I recommend treatment if the neutrophil count is <1000.
Guidelines for treatment include:
- Neutrophil count <1,500/uL, no fever or clinical signs (lethargy, anorexia, V/D), delay therapy for 2-4 days and repeat CBC prior to chemotherapy.
- Neutrophil count <1000/uL, no fever or clinical signs (lethargy, anorexia), delay therapy for 7 days, administer prophylactic fluroquinolone antibiotics, and repeat CBC prior to chemotherapy. Subsequent drug dosage may be decreased by 10-20%.
- Neutrophil count <1000/uL and fever or signs consistent with sepsis, hospitalize and treat appropriately and aggressively. For febrile and clinically ill animals, assume sepsis is present and treat with broad-spectrum intravenous antibiotics covering gram-positives (for skin bacteria), gram-negatives (for gastrointestinal bacteria), and anaerobes (for oral bacteria). The patient should also be supported with intravenous fluids and other supportive care measures. The use of recombinant human colony-stimulating factors (Neupogen®) is occasionally considered in select cases. Death from chemotherapy-induced sepsis is low especially with early and aggressive therapy; it occurs in <5% of patients in my experience. Subsequent drug dosage should be decreased by 20-25%.
- Chemotherapy should be delayed when the platelet count is <50,000/uL. Patients should be monitored for signs of mucosal bleeding when the count is <30,000/uL.
Certain chemotherapy drugs can cause allergic reactions. Doxorubicin can cause an allergic reaction which is usually characterized by head-shaking, urticarial, erythema of the ears/skin, vocalization, vomiting, Certain chemotherapy drugs can cause allergic reactions. Doxorubicin can cause an allergic reaction which is usually characterized by head-shaking, urticarial, erythema of the ears/skin, vocalization, vomiting, flatulence, tachycardia or tachypnea. These reactions occur during the administration or shortly thereafter. If any of these symptoms occur, the injection should be stopped and the patient should be administered IV fluids (0.9% NaCl), diphenhydramine (2 mg/kg IM), and dexamethasone SP (0.2 mg/kg IM or IV). After 30 minutes the infusion can be restarted. The patient should be pretreated for every future doxorubicin treatment. I recommend pretreating the diphenhydramine and dexamethasone SP in these patients.
L-asparaginase (elspar) can also cause a hypersensitivity reaction in dogs and cats. Elspar is an enzyme produced by bacteria; it is inherently a foreign protein and as such can produce an allergic reaction. Allergic reactions are reported to occur in <2% of l-asparaginase doses administered. The clinical signs are similar to those described above for doxorubicin. Hypersensitivity reactions to l-asparagainse usually occur between 30 minutes and 4 hours after treatment. To reduce the risk, an injection of diphenhydramine (2 mg/kg IM) about 30 minutes prior to treatment is an option. Once a patient has received a dose of l-asparaginase, I pretreat for all subsequent treatments.
